The objects of the present study were: (1) to define the relationships of the arachnoid mater to blood vessels in the subarachnoid space; (2) to establish the structure of leptomeningeal trabeculae and their relationships to the pia mater; and (3) to investigate the fine structure of the human pia mater. Intracranial portions of vertebral artery were taken at post mortem, and normal cerebral cortex and overlying leptomeninges were obtained from surgical lobectomies. Tissue from these specimens was examined by scanning and transmission electron microscopy, by light microscopy and by immunocytochemistry for the presence of basement membrane, desmosomal proteins and vimentin. Results of the study showed that as the vertebral artery pierced the posterior atlanto-occipital membrane and entered the subarachnoid space, it acquired a leptomeningeal coat as the arachnoid was reflected on to it. It has been demonstrated previously that as vessels enter the brain, the leptomeningeal coat is reflected on to the surface of the cortex as the pia mater. The arachnoid mater was seen to consist of a subdural mesothelial layer and a compact central layer as previously reported. From the inner layer of the arachnoid, collagen bundles coated by leptomeningeal cells extended as trabeculae across the subarachnoid space to fuse with the pia mater. The pia itself was composed of a delicate but apparently continuous layer of cells joined by desmosomes and gap junctions but no tight junctions were observed. It was possible to detect pia mater cells in the perivascular spaces of the brain by immunocytochemical techniques using light microscopy. The significance of the observed anatomical arrangement for cerebrospinal fluid physiology is discussed.

In liver fibrosis and cirrhosis there is a change in both the Liver fibrosis results from a relative imbalance beamount and relative composition of the hepatic extracellular tween synthesis and degradation of matrix proteins. We matrix. 1 Current evidence suggests that hepatic stellate cells have previously described release of the potent collagen-(lipocytes, fat-storing or Ito cells) are central to this process ase inhibitor, tissue inhibitor of metalloproteinase-1 both as the major source of fibrillar and nonfibrillar matrix (TIMP-1), by culture-activated human hepatic stellate proteins and matrix degrading metalloproteinases. 1-11 cells (HSCs). In this study, we have investigated the relaWe have previously shown that cultured hepatic stellate tive expression of TIMP-1 and interstitial collagenase in cells (HSCs) activated to a myofibroblastic phenotype express culture-activated rat HSCs and rat models of liver injury gelatinase A (72-kd type IV collagenase/gelatinase) 12,13 and and fibrosis. The complementary DNA (cDNA) for rat there is evidence to suggest that they also secrete stromely-TIMP-1 was obtained by homology polymerase chain reaction (PCR) and sequenced. By Northern analysis using sin. 14 A further metalloproteinase, interstitial collagenase, this probe, TIMP-1 messenger RNA (mRNA) expression expressed by mesenchymal and other cell types has degradawas up-regulated with HSC activation by culture on tive activity against native collagen types I and III, 15,16 explastic as defined by cellular expression of procollagen-pression of which could potentially initiate remodelling of 1. Interstitial collagenase mRNA was expressed in early fibrotic liver. culture (õ4 days) but became undetectable in more actiInterstitial collagenase expression in liver has been varivated cells (7-21 days). By activity assay of serum-free ously ascribed to parenchymal and sinusoidal liver cells, incell-conditioned media, TIMP-1 was found to be released cluding Kupffer cells 17,18 and hepatocytes. 19,20 There is also in increasing concentrations with duration of culture on some evidence to indicate that HSCs are a cellular source of plastic. Expression of TIMP-1, interstitial collagenase, interstitial collagenase in liver; studies on a passaged celland procollagen-1 mRNAs were studied in rat models of line derived by outgrowth from human liver (of possible HSC biliary and parenchymal injury (bile duct ligation and origin) showed that interstitial collagenase is expressed conCCl 4 administration) by ribonuclease protection assay. stitutively and is up-regulated in response to interleukin-TIMP-1 mRNA expression was increased at 6, 24 hours, 1 and tumor necrosis factor a. 21 Li et al. have also shown and 3 days after bile duct ligation and was also shown collagenase activity in cultured rat HSCs which was into rise in acute CCl 4 liver injury and remain elevated as creased in response to polyunsaturated lecithin. 22 the liver became fibrotic. TIMP-1 expression precededIn studies undertaken to measure interstitial collagenase proc...

1. Liver fibrosis is a common sequel to diverse liver injuries. It is characterized by an accumulation of interstitial collagens and other matrix components. The hepatic stellate cell is pivotal to the pathogenic process. Fibrotic liver injury results in activation of the hepatic stellate cell which undergoes a phenotypic change to a proliferative myofibroblast-like cell which synthesizes excess interstitial collagens and other matrix components. 2. The process of initiation of activation and its perpetuation result from complex, often interrelated series of signalling mechanisms which converge on this effector cell. Such mechanisms include alterations in matrix resulting in changed cell-matrix interactions and stimulation by cytokines released from damaged hepatocytes, infiltrating inflammatory cells, Kupffer cells and matrix. Foremost among the profibrotic cytokines is transforming growth factor beta 1. 3. Once the hepatic stellate cell is activated the preceding matrix changes and recurrent injurious stimuli will perpetuate the activated state. 4. Despite the accumulation of excess collagens, the liver retains a capacity for matrix degradation. This capacity may be overwhelmed and any secreted matrix remodelling enzymes may be inhibited by the concurrently secreted tissue inhibitors of metallo-proteinase-1 and alpha 2-macroglobulin. 5. Our understanding of the molecular pathogenesis of liver fibrosis is increasing. It is anticipated that this knowledge will provide novel therapeutic avenues to treat this disease process.

Objective-To assess the family history ofdiabetes in non-insulin dependent diabetes mellitus with particular emphasis on parental phenotype.Design-Family histories were obtained from an existing computerised database and supplemented by postal questionnaires.Setting-Diabetic service of a provincial teaching hospital.Subjects-A total of 1326 patients with non-insulin dependent diabetes who had been referred to diabetic clinics over the past 10 years and from whom data had been collected for inclusion in the database, of whom 347 had affected first degree relatives. Nineteen non-white patients were excluded because of the differential hereditability of the disease, and 230 (70%) patients with an affected first degree relative responded to the postal questionnaire.Results-Mothers were implicated in significantly more cases than fathers in patients with a single affected parent: 125 mothers and 48 fathers from database; 82 mothers and 34 fathers from postal questionnaire; p<0 001 in both cases.Conclusions-Maternal influences seem to have an important role in the inheritance of non-insulin dependent diabetes. IntroductionThe genetics of non-insulin dependent diabetes mellitus remains an enigma. It is well known that many patients give a positive family history, but attempts to place the disease into the simple mendelian pattern have failed. Furthermore, molecular genetic studies have not been as successful in finding disease markers as in insulin dependent diabetes.' Several recent studies have suggested that intrauterine environment may also predispose to the development of non-insulin dependent diabetes.2 This would further complicate the transmission pattern of the disease by simulating genetic inheritance through maternal transmission. To clarify the genetics of non-insulin dependent diabetes and the role of maternal inheritance we studied the family history of a large number of patients with noninsulin dependent diabetes.

Infliximab is a monoclonal antibody against tumour necrosis factor-alpha. Recent studies have shown that it is effective in treating patients with refractory Crohn’s disease and in those with Crohn’s fistulae. Though this drug is found to be safe in clinical trials, sporadic reports of serious complications have been recorded in the literature. The case of a patient who developed profuse genital warts after infliximab treatment is reported. The literature is reviewed and information is presented on side effects and complications as a result of infliximab therapy.